The basic objectives of this proposal are to make creative contributions to the total synthesis of alkaloid natural products of high physiological activity. Targets for synthesis include perhydrohistrionicotoxin, the tropolone alkaloids colchicine and imerubrine, tylophora alkaloids, morphine, and the antibiotic naphthyridinomycin. Many of the alkaloids listed above are either cytotoxic or neurotoxic bases of considerable interest as potential chemotherapeutic agents. During the course of this project we intend to develop new synthetic methods of general applicability to alkaloid synthesis.